An understanding of the mechanism of action of antiarrhythmic drugs requires that the factors responsible for the arrhythmias be understood. The objectives of the proposed research are to gain a more complete insight into: 1) the electrophysiologic factors, particularly slowed conduction, involved in arrhythmia production, 2) the precise correlation between the metabolic consequences of ischemia and these electrophysiologic abnormalities, 3) the relationships between changes in the single cell and changes in the intact heart and 4) the influence of antiarrhythmic drugs on the metabolic and electrophysiologic changes. To accomplish these objectives we propose studying single fibers and intact hearts utilizing microelectrode and intracardiac recording techniques and ion specific macro and microelectrodes. The single fiber studies will be directed towards gaining a better understanding of the factors responsible for conduction and the effect of modelled ischemia on these parameters. In the intact heart we will attempt to catetorize the correlation between metabolic and electrical changes. In both the single fiber and intact heart experiments, we will determine, if time permits, the effects of antiarrhythmic drugs on these factors. It is hoped that the results of the proposed study will contribute to our understanding of the ischemic process and to our ability to prevent and treat ischemia related arrhythmias.